Phenotypes associated with this allele

• Allele Symbol: Slc4a1^tm1Llp
• Allele Name: targeted mutation 1, Luanne L Peters
• Allele ID: MGI:1857140
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Slc4a1^tm1Llp/Slc4a1^tm1Llp	B6;129S4-Slc4a1^tm1Llp/J	MGI:3714742
hm2	Slc4a1^tm1Llp/Slc4a1^tm1Llp	involves: 129S4/SvJae * C57BL/6J	MGI:2672144
ht3	Slc4a1^tm1Llp/Slc4a1^+	involves: 129S4/SvJae * C57BL/6J	MGI:3844316
ht4	Slc4a1^tm1Llp/Slc4a1^wan	involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J	MGI:3027983

Genotype
MGI:3714742

hm1

• Allelic Composition: Slc4a1^tm1Llp/Slc4a1^tm1Llp
• Genetic Background: B6;129S4-Slc4a1^tm1Llp/J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

postnatal lethality, incomplete penetrance ( J:120610 )

• more than 90% die within the first week after birth; those that survive the firsts week reach adulthood

growth/size/body

cardiac hypertrophy ( J:120610 )

• heart weight-to-body weight ratio is increased by abut 50%, indicating cardiac hypertrophy

decreased body size ( J:120610 )

decreased body weight ( J:120610 )

• body weight is reduced to 50% and 55% of wild-type at 1-3 days of age and 1 week of age, respectively

hematopoietic system

hemolytic anemia ( J:120610 )

• severe

decreased hematocrit ( J:120610 )

• hematocrit drops to 18% compared to 48% in wild-type

spherocytosis ( J:120610 )

cardiovascular system

abnormal heart shape ( J:120610 )

• hearts are misshapen

cardiac hypertrophy ( J:120610 )

• heart weight-to-body weight ratio is increased by abut 50%, indicating cardiac hypertrophy

dilated heart left ventricle ( J:120610 )

cardiac interstitial fibrosis ( J:120610 )

• disperse interstitial fibrosis, manifested by an increase in collagen deposition and thickness of collagen fibers, in the left ventricle; fibrosis is not seen in the right ventricle

decreased ventricle muscle contractility ( J:120610 )

• ventricle dilation in both the systolic and diastolic phases, an increase in the left ventricular end-diastolic dimension and end-systolic dimension, and a 2-fold decrease in shortening fraction

increased heart rate ( J:120610 )

muscle

decreased ventricle muscle contractility ( J:120610 )

• ventricle dilation in both the systolic and diastolic phases, an increase in the left ventricular end-diastolic dimension and end-systolic dimension, and a 2-fold decrease in shortening fraction

integument

pallor ( J:120610 )

• pale at birth, particularly in the prominent white abdominal band

cellular

cardiac interstitial fibrosis ( J:120610 )

• disperse interstitial fibrosis, manifested by an increase in collagen deposition and thickness of collagen fibers, in the left ventricle; fibrosis is not seen in the right ventricle

Genotype
MGI:2672144

hm2

• Allelic Composition: Slc4a1^tm1Llp/Slc4a1^tm1Llp
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:148154 )

• oral acid loading for more than 24 hours resulted in death from apparent dehydration and massive hemolysis

premature death ( J:148154 )

• about 16% survival at 10 to 14 weeks of age from crosses of homozygous males to heterozygous females

postnatal lethality, incomplete penetrance ( J:35487 )

• 85% of animals die within two weeks of birth

renal/urinary system

abnormal urine homeostasis ( J:148154 )

• hypocitraturia is seen at 12 weeks of age

increased urine calcium level ( J:148154 )

• seen at 12 weeks of age

decreased urine osmolality ( J:148154 )

increased urine pH ( J:148154 )

• alkaline urine with reduced excretion of net acid and titratable acids

kidney medulla atrophy ( J:148154 )

• reduction in inner medullary mass resembling that in chronic hydronephrosis

• inner medullary atrophy with a compensatory increase in abundance of outer medullary AQP2

nephrocalcinosis ( J:148154 )

• nephrocalcinosis indicted by predominantly medullary calcium phosphate deposits

• however, formation of calculi (nephrolithiasis) is not detected

abnormal kidney physiology ( J:148154 )

• modest decrease in acidification rate of cultured type A intercalated cells following chloride readdition to a chloride free bath

• acidification of cultured type A intercalated cells is insensitive to diBA(5)C4 and shows reduced sensitivity to 4-4'-diisothiocyanatostilbene-2,2'-disulfonic acid suggesting upregulation of pharmacologically distinct anion exchange activity

decreased creatinine clearance ( J:148154 )

• oral acid loading results in decreased creatinine clearance probably reflecting systemic dehydration

polyuria ( J:148154 )

• 24 hour urine output is increased 2 to 4 fold compared to controls

homeostasis/metabolism

abnormal blood homeostasis ( J:148154 )

increased blood osmolality ( J:148154 )

• increase in serum osmolarity is seen at 12 weeks of age suggesting mild systemic dehydration

• oral acid loading greatly increases plasma osmolarity without altering urinary osmolality

acidemia ( J:148154 )

• low blood pH seen at 12 weeks of age

increased blood urea nitrogen level ( J:148154 )

• seen at 12 weeks of age

decreased circulating bicarbonate level ( J:148154 )

• low blood bicarbonate levels seen at 12 weeks of age

increased circulating phosphate level ( J:148154 )

• slight increase at 12 weeks of age

dehydration ( J:148154 )

• oral acid loading induces systemic dehydration

increased circulating chloride level ( J:148154 )

• slight increase at 12 weeks of age

metabolic acidosis ( J:148154 )

• severe metabolic acidosis with low blood pH and bicarbonate levels is seen in 12 week old mice

• challenge with oral acid loading disproportionately worsens metabolic acidosis compared to similarly treated wild-type or heterozygous controls

abnormal urine homeostasis ( J:148154 )

• hypocitraturia is seen at 12 weeks of age

increased urine calcium level ( J:148154 )

• seen at 12 weeks of age

decreased urine osmolality ( J:148154 )

increased urine pH ( J:148154 )

• alkaline urine with reduced excretion of net acid and titratable acids

increased susceptibility to xenobiotic induced morbidity/mortality ( J:148154 )

• oral acid loading for more than 24 hours resulted in death from apparent dehydration and massive hemolysis

hematopoietic system

enlarged spleen ( J:35487 )

• spleens are 15 times larger in homozygotes than in littermates

abnormal definitive hematopoiesis ( J:35487 )

microcytic anemia ( J:35487 )

• severe hemolytic anemia noted in animals surviving to adulthood

absent erythroid progenitor cell ( J:85321 )

• incomplete penetrance; reticulocytes are seen in only 2 of 12 newborn mice tested

abnormal proerythroblast morphology ( J:85322 )

• presence of binucleated erythroblasts; 4% of mice compared to < 1% of wild-type mice

abnormal erythrocyte morphology ( J:35487 )

decreased erythrocyte cell number ( J:35487 )

decreased hematocrit ( J:35487 , J:148154 )

• severely decreased in mice at 5 - 7 days and 14 weeks of age (J:148154)

decreased hemoglobin content ( J:35487 )

abnormal mean corpuscular hemoglobin ( J:35487 )

• decreased hemoglobin content

decreased mean corpuscular volume ( J:35487 )

increased nucleated erythrocyte cell number ( J:35487 )

• nucleated erythroid cells are found in circulation

hyperchromasia ( J:35487 )

microcytosis ( J:35487 )

poikilocytosis ( J:35487 )

polychromatophilia ( J:35487 )

spherocytosis ( J:35487 )

reticulocytosis ( J:35487 , J:148154 )

• greater than 70% reticulocytosis in mice at 5 - 7 days of age (J:148154)

hemolysis ( J:148154 )

• oral acid loading induces severe hemolysis

growth/size/body

weight loss ( J:148154 )

• oral acid loading results in loss of 14% of initial body weight within 24 hours

postnatal growth retardation ( J:35487 )

• noted in animals surviving to adulthood

slow postnatal weight gain ( J:148154 )

• survivors grow more slowly

enlarged spleen ( J:35487 )

• spleens are 15 times larger in homozygotes than in littermates

immune system

enlarged spleen ( J:35487 )

• spleens are 15 times larger in homozygotes than in littermates

integument

pallor ( J:35487 )

• pale appearace noted at birth

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
renal tubular acidosis		DOID:14219	OMIM:179830 OMIM:267200 OMIM:602722	J:148154

Genotype
MGI:3844316

ht3

• Allelic Composition: Slc4a1^tm1Llp/Slc4a1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

homeostasis/metabolism

abnormal physiological response to xenobiotic ( J:148154 )

• fail to show wild-type urinary concentration response to oral acid loading

Genotype
MGI:3027983

ht4

• Allelic Composition: Slc4a1^tm1Llp/Slc4a1^wan
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J

hematopoietic system

reticulocytosis ( J:85321 )